We tested the cross-ancestry polygenic risk score (PRS) association with AUDIT–P in UKB using AUD summary data from EUR (leaving out the UKB AUDIT–P data), AFR and LA. PRS-CSx38 was applied to calculate the posterior effect sizes for each SNP by leveraging LD diversity across discovery samples. We validated the PRS associations with AUDIT–P in UKB–EUR2 and tested them in UKB–EUR1 (Table 1). In the UKB–EUR1 samples, the EUR-based AUD PRS was significantly associated with AUDIT–P (Z score 11.6, P = 3.14 × 10−31, covariate-adjusted R2 = 3.31% and ΔR2 = 0.11%). By incorporating GWAS data from multiple ancestries, the AUD PRS was more significantly associated with AUDIT–P and explains more variance (Z score 13.6, P = 2.44 × 10−42, covariate-adjusted R2 = 3.35% and ΔR2 = 0.15%) than the single-ancestry AUD PRS.
